The essential role of the in situ immune reaction in human colorectal cancer

Empty spiracles homeobox 2 (EMX2) is a homeodomain-containing transcription factor that plays an essential role in tumorigenesis. However, to the best of our knowledge, the role of EMX2 in human colorectal cancer (CRC) is still unclear. Thus, the aim of this study was to investigate the expression and role of EMX2 in CRC. Our results demonstrated that the expression of EMX2 was greatly decreased in CRC tissues and cell lines. Overexpression of EMX2 significantly inhibited the proliferation in vitro and CRC tumor growth in nude mice. In addition, EMX2 also inhibited the migration and invasion of CRC cells. Mechanically, overexpression of EMX2 downregulated the expression levels of β-catenin, cyclin D1, and c-Myc in CRC cells. Taken together, our study demonstrates that EMX2 inhibits proliferation and tumorigenesis through inactivation of the Wnt/β-catenin pathway in CRC cells. Therefore, EMX2 may be a potential therapeutic target for the treatment of CRC.

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Mechanisms of genomic instability in human colorectal cancer: the role of signaling by Integrin-Linked-Kinase (ILK)

10.26226/morressier.5b4709896f4cb30010951e42 ◽

2018 ◽

Author(s):

Sofia Nikou ◽

Chadla Panagiota

Keyword(s):

Colorectal Cancer ◽

Genomic Instability ◽

Human Colorectal Cancer ◽

Integrin Linked Kinase

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The essential role of TAp73 in bortezomib-induced apoptosis in p53-deficient colorectal cancer cells

Scientific Reports ◽

10.1038/s41598-017-05813-z ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 19

Author(s):

Yasamin Dabiri ◽

Sara Kalman ◽

Clara-Marie Gürth ◽

Jee Young Kim ◽

Viola Mayer ◽

...

Keyword(s):

Colorectal Cancer ◽

Cancer Cells ◽

Essential Role ◽

Colorectal Cancer Cells ◽

Induced Apoptosis

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Assessment of TRPV4 Channel and Its Role in Colorectal Cancer Cells

Biomedical & Pharmacology Journal ◽

10.13005/bpj/1683 ◽

2019 ◽

Vol 12 (2) ◽

pp. 629-638

Author(s):

N. N. Bahari ◽

S. Y. N. Jamaludin ◽

A. H. Jahidin ◽

M. N. Zahary ◽

A. B. Mohd Hilmi

Keyword(s):

Colorectal Cancer ◽

Cell Cycle ◽

Cell Death ◽

Cancer Cells ◽

Human Colorectal Cancer ◽

Expression Levels ◽

Pharmacological Modulation ◽

Colorectal Cancer Cells ◽

Ht 29

The transient receptor potential vanilloid member 4 (TRPV4) is a non-selective calcium (Ca2+)-permeable channel which is widely expressed in different types of tissues including the lungs, liver, kidneys and salivary gland. TRPV4 has been shown to serve as a cellular sensor where it is involved in processes such as osmoregulation, cell volume regulation and thermoregulation. Emerging evidence suggests that TRPV4 also plays important roles in several aspects of cancer progression. Despite the reported roles of TRPV4 in several forms of cancers, the role of TRPV4 in human colorectal cancer remains largely unexplored. In the present study, we sought to establish the potential role of TRPV4 in colorectal cancer by assessing TRPV4 expression levels and investigating whether TRPV4 pharmacological modulation may alter cell proliferation, cell cycle and cell death in colorectal cancer cells. Quantitative real-time PCR analysis revealed that TRPV4 mRNA levels were significantly lower in HT-29 cells than normal colon CCD-18Co cells. However, TRPV4 mRNA was absent in HCT-116 cells. Pharmacological activation of TRPV4 with GSK1016790A significantly enhanced the proliferation of HT-29 cells while TRPV4 inhibition using RN 1734 decreased their proliferation. Increased proliferation in GSK1016790A-treated HT-29 cells was attenuated by co-treatment with RN 1734. Pharmacological modulation of TRPV4 had no effect on the cell cycle progression but promoted cell death in HT-29 cells. Taken together, these findings suggest differential TRPV4 expression levels in human colorectal cancer cells and that pharmacological modulation of TRPV4 produces distinct effects on the proliferation and induces cell death in HT-29 cells.

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Increased in situ expression of nitric oxide synthase in human colorectal cancer

Virchows Archiv ◽

10.1007/pl00008208 ◽

2000 ◽

Vol 436 (2) ◽

pp. 109-114 ◽

Cited By ~ 72

Author(s):

N. Yagihashi ◽

H. Kasajima ◽

S. Sugai ◽

K. Matsumoto ◽

Y. Ebina ◽

...

Keyword(s):

Nitric Oxide ◽

Colorectal Cancer ◽

Nitric Oxide Synthase ◽

Human Colorectal Cancer ◽

Oxide Synthase

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Long-term maintenance capecitabine and celecoxib improved clinical outcomes by targeting colorectal cancer micrometastasis

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14513 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14513-14513

Author(s):

M. Zhang ◽

S. Curley ◽

C. Ng ◽

B. Kurland ◽

S. Krishnan ◽

...

Keyword(s):

Colorectal Cancer ◽

Stage Iv ◽

Complete Response ◽

Kaplan Meier ◽

Stage Iv Disease ◽

Disease Site ◽

Colorectal Cancer Patients

14513 Background: Role of mainteance therapy after achieving complete response (CR) remain undefined for patients with metasatic colorectal cancer. We studied prognostic and treatment factors including maintenance capecitabine and celecoxib (XCEL) in all 19 unresectable metastatic colorectal cancer patients (pts) who had CR from the prior XCEL study. Methods: Event charts are used to summarize the timeline of the various treatments. Kaplan-Meier survival estimates and univariate log-rank tests were used to evaluate RFS and OS as time from CR. Prognostic and treatment factors included: tumor size, metastasis number (9 solitary disease), site (13 being extrahepatic), stage on diagnosis (stage II versus III/IV), disease free interval prior to stage IV disease, surgery (5 R0, 3 R1–2 resections), lactate dehydrogenase levels, first-line irinotecan chemotherapy, radiation (9 pts ≥ 45 Gy, 3 Pts < 45 Gy), and maintenance XCEL (duration 0–50.3 months). Results: Nine of 19 patients experienced recurrence (median 13 months after CR), and 4 died during the follow-up period (median 31 months after CR). The 2-year RFS for the unresected and R1–2 resected patients was 71% versus 20% for the R0 resected patients (p = 0.07). This paradoxical RFS pattern corresponded to a RFS advantage for maintenance XCEL (p = 0.002), but not any other prognostic or treatment factors. All relapses occurred in situ following discontinuation of XCEL except for the surgical cases. Patients undergoing maintenance XCEL also benefited in OS (p = 0.04). The median OS from XCEL and from onset of metastasis reached 51.9 months (95% CI, 45 months- not reached [NR]) and 73.3 months (95% CI, NR-NR months) respectively. Conclusions: Maintenance XCEL targets colorectal micrometastases and produces a paradoxical RFS and OS advantage among the high-risk unresected/R1–2 resected patients than R0 resected patients. Prospective studies are warranted to validate roles of maintenance XCEL in the treatment of colorectal micrometastases. No significant financial relationships to disclose.

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